The Center of Research Excellence in Natural Products Neuroscience (CORE-NPN) at The University of Mississippi School of Pharmacy (UM), initiated four years ago through a COBRE grant, has developed a multidisciplinary team committed to evaluating the effects of natural products on the central nervous system (CNS). The Center now has the potential to develop and sustain an innovative and independently funded research center focused on treating disorders associated with the nervous system. Faculty in the Center and its academic home, the School of Pharmacy, have already reported groundbreaking observations on the roles of cannabinoids and non-cannabinoids in the etiology of weight control, the control of the immune system, treatment of cancer, control of nausea and vomiting in patients receiving anti-neoplastic treatment, glaucoma, and the development of sigma receptor agonists in the treatment of cocaine and methamphetamine abuse. Also, CORE-NPN-supported investigators have increased their competitiveness by attracting extramural funds and publishing in leading journals of neuroscience. The Center will continue to provide an excellent environment for junior and mid-level investigators by working in close collaboration with leading national centers and scientists studying natural products to carry out the proposed projects that build on these novel insights into the pathophysiology of nervous system disorders. To achieve the goal of establishing an innovative and multidisciplinary Center focused on the use of natural products to manage neuropharmacologic disorders, the following Specific Aims are proposed: Aim 1 is to enhance the competitive independent research funding of four investigators, as detailed in their research proposals. In addition, external and internal renowned scientists in natural products neuroscience will continue to mentor all Center faculty members in basic and clinical neuroscience. Aim 2 is to sponsor a competitive small grant program that advances research in neuroscience related to the themes outlined in the proposal. Aim 3 is to continue the expansion of research resources for the development of innovative natural product neuropharmacology - related projects. Core facilities to accomplish this will include: a) acquisition of novel plants and fungi and isolation of biologically active natural products, b) chemical elucidation of the biologically active secondary metabolites and synthesis of derivatives, c) in vitro assays to identify biologically active natural products, and d) in vivo assays to evaluate behavioral studies of the biologically active natural products. Aim 4 is to continue faculty development and growth of new neuroscience investigators through training in cutting-edge technologies and to promote research opportunities in neuroscience for undergraduate and graduate students being mentored by Center faculty.